Zinc finger protein 191 inhibits hepatocellular carcinoma metastasis through discs large 1‐mediated yes‐associated protein inactivation

• DOI: 10.1002/hep.28708
• Publication Date: 2016-06-30T08:48:59Z
• Authors: Di Wu; Guoyuan Liu; Yufeng Liu; Hexige Saiyin; Chenji Wang; Zhen Wei; Wenjiao Zen; Danyang Liu; Qi Chen; Zhonghua Zhao; Liping Zou; Haojie Huang; Songmin Jiang; Long Yu
• Keywords: Metastasis suppressor; Cell polarity; Chromatin immunoprecipitation; Crosstalk

Interplay between cell polarity module Scribble‐Lethal Giant Larvae‐Discs Large 1 (DLG1) and Yes‐associated protein (YAP) appears critical in tumor metastasis. We identified zinc finger 191 (ZNF191) as a metastasis suppressor acting through DLG‐YAP crosstalk hepatocellular carcinoma (HCC). Overexpression of ZNF191 HCC cells impaired motility, while depletion promoted migration vitro vivo triggering YAP signaling. Chromatin immunoprecipitation‐sequencing revealed that specifically bound to the promoter DLG1, maintainer negative regulator YAP. The binding sequence at DLG1 is seven‐repeat TCAT motif. Double‐knockdown experiments inferred was not only mediator function suppress but also link Decreased expression human metastatic specimens correlated positively with levels inversely activation. Our findings illustrate YAP‐targeting, antimetastasis ZNF191, thereby representing possible prognostic marker potential target for therapy. Conclusion: directly binds typical repeating motif activates DLG1; up‐regulating inhibits activation eventually . (H epatology 2016;64:1148‐1162)